Rare最新文献

{"title":"Abstracts of the 2023 UDNI Conference","authors":"","doi":"10.1016/j.rare.2024.100055","DOIUrl":"10.1016/j.rare.2024.100055","url":null,"abstract":"","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of social deprivation as a modifier of phenotypic divergence in PTEN Hamartoma Tumor Syndrome","authors":"Parker L. Bussies ,&nbsp;David Bruckman ,&nbsp;Lamis Yehia ,&nbsp;Takae Mizukami ,&nbsp;Karen Hurley ,&nbsp;Jarrod Dalton ,&nbsp;Charis Eng","doi":"10.1016/j.rare.2024.100053","DOIUrl":"10.1016/j.rare.2024.100053","url":null,"abstract":"<div><div>Pathogenic mutations in phosphatase and tensin homolog (<em>PTEN</em>), a tumor suppressor gene, leads to the development of <em>PTEN</em> Hamartoma Tumor Syndrome (PHTS). Patients carry significantly increased risks for cancer and neurodevelopmental disorders such as autism spectrum disorder (ASD). The factors which modify <em>PTEN</em> function and drive PHTS phenotype remain unknown. Social determinants of health are increasingly being identified as important regulators of disease pathogenesis. Here, we conduct a retrospective cross-sectional study to evaluate the association between social deprivation, as measured by area deprivation index (ADI), and neurodevelopmental versus cancer phenotypes in patients with PHTS. Our findings suggest ADI alone is not associated with PHTS phenotype, and that its divergence is likely multifactorial in nature. More broadly, our study highlights the importance of integrating environmental pressures with genetic risk modification in the study of complex human disease.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The BeWayAPDS project: Designing the best way to optimize management of activated PI3Kδ syndrome (APDS) in Spain from the perspective of key stakeholders","authors":"María Elena Seoane-Reula ,&nbsp;Carmen Garrido-Colino ,&nbsp;Inmaculada Mediavilla ,&nbsp;Laia Alsina ,&nbsp;Miguel García ,&nbsp;Jose Luis Poveda ,&nbsp;Carlos Mur ,&nbsp;Sandra Flores ,&nbsp;Carmen Alerany ,&nbsp;María Ángeles Escobar Palazón ,&nbsp;Carlos Jiménez ,&nbsp;Macarena Sierra ,&nbsp;Kirsten H. Herrmann ,&nbsp;Alicia Gil","doi":"10.1016/j.rare.2025.100071","DOIUrl":"10.1016/j.rare.2025.100071","url":null,"abstract":"<div><h3>Background</h3><div>Rare diseases represent a challenge for healthcare systems due to lack of awareness, complexity in management and the limited published evidence available. Activated phosphoinositide 3-kinase delta syndrome (APDS) involves different healthcare specialists from diagnosis to long-term follow-up. Being an ultra-rare chronic complex disorder categorized within inborn errors of immunity (IEI) without clinical guidelines or disease modifying treatments, several challenges arise in patient management. This study aims to elucidate current diagnosis and management processes, identify challenges and opportunities and design a patient pathway directed at improving patient outcomes.</div></div><div><h3>Methods</h3><div>A literature review was performed to develop a questionnaire to obtain evidence through individual interviews with a multistakeholder panel of experts. A patient pathway was proposed by the experts, including main challenges encountered through management of APDS and proposing potential practical solutions. Challenges were prioritised, identifying those with the highest potential to improve patient management. The proposed patient pathway and the prioritisation of challenges and solutions were then discussed in a reflective group discussion.</div></div><div><h3>Results</h3><div>A patient pathway was designed and validated including diagnosis, short- and long-term follow-up. Challenges identified impact different steps of the pathway, affecting optimal disease diagnosis, management and outcomes. The solutions proposed included the constitution of IEI multidisciplinary teams, early diagnosis in the symptomatic phase, development of an APDS treatment guideline/algorithm, implementation of artificial intelligence (AI) tools to support diagnosis, training in IEI in Primary Care (PC) centres and reinforcement of patient experience and perspective in decision-making.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare homozygous CNPY3 variant causing autosomal recessive developmental and epileptic encephalopathy 60: A case report","authors":"Nohela Rehman ,&nbsp;Zohra Hasan Ali ,&nbsp;Mahrukh Nasir ,&nbsp;Salman Kirmani","doi":"10.1016/j.rare.2025.100081","DOIUrl":"10.1016/j.rare.2025.100081","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Epilepsy is one of the most common neurological disorders, affecting around 50 million people globally. Developmental and epileptic encephalopathy 60 (DEE60) is an autosomal recessive disorder caused by mutations in the Canopy FGF signaling regulator 3 (&lt;em&gt;CNPY3&lt;/em&gt;) gene. Symptoms start in infancy and include developmental delay, seizures, and myoclonus, with EEGs showing hypsarrhythmia indicative of West syndrome. &lt;em&gt;CNPY3&lt;/em&gt; is crucial for Toll-like receptor chaperoning and can potentially cause neuronal circuit imbalances. This report examines the first reported instance of DEE60 in Pakistan with a missense mutation in the &lt;em&gt;CNPY3&lt;/em&gt; gene, aiming to advance the current literature on &lt;em&gt;CNPY3&lt;/em&gt; and bring attention to a rare condition that currently only has symptomatic treatment. Only five cases have been reported globally.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methodology&lt;/h3&gt;&lt;div&gt;Informed consent was obtained from the patient’s parents for the publication of this study and patient confidentiality has been maintained such that no data in the submission can reveal the patient's identity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Case presentation&lt;/h3&gt;&lt;div&gt;A 5-month-old male, born of consanguineous parents, presented to the Aga Khan University Hospital with severe seizures, a history of global developmental delay and a family history of seizures. The patient had his first seizure at 3 months and was started on antiseizure medications. He was born full-term via caesarean section, requiring oxygen support postnatally due to delayed cry and cyanosis. He exhibited delayed developmental milestones, low interaction levels, unresponsiveness to loud sounds and no smiling since birth. Systemic examinations were normal, but MRI and EEG findings suggested West Syndrome, DEE, and inborn errors of metabolism (IEM). Whole exome sequencing (WES) revealed a homozygous likely pathogenic variant in the &lt;em&gt;CNPY3&lt;/em&gt; gene (NM_006586.5) c.275 C&gt;T (p.Ser92Leu, rs556172653), confirming DEE60. At follow-up, the patient experienced increased seizure frequency, intermittent fever, recurrent chest infections and decreased muscle tone. Management included anti-seizure medications, benzodiazepines, anticonvulsants, neurobiotin, folic acid, vitamin B and ACTH. The parents were counselled about DEE60, prenatal testing, and a 25 % occurrence of recessive disorders. There is currently no gene therapy for this condition.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Comment&lt;/h3&gt;&lt;div&gt;The variant reported in dataebases is predicted to be deleterious, consistent with the phenotype observed in our patient. ClinVar records 34 &lt;em&gt;CNPY3&lt;/em&gt; variants with 20 variants of uncertain significance. This highlights the need for further research to understand &lt;em&gt;CNPY3&lt;/em&gt;-associated phenotypes and its role in neuronal activity. Improved newborn and genetic testing access in Pakistan is essential for timely diagnosis and management, given the high costs of foreign labs and the risk of undiagnosed cases.&lt;/d","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidental findings in surveillence of paediatric Li Fraumeni patients – A single centre experience","authors":"Amy Alcock ,&nbsp;Elizabeth McVittie ,&nbsp;Zoe Nicholls ,&nbsp;Hector Conti ,&nbsp;Mark Davies ,&nbsp;Rhian Isaac ,&nbsp;Madeleine Adams ,&nbsp;on behalf of the All Wales Paediatric Cancer Predisposition Service","doi":"10.1016/j.rare.2025.100067","DOIUrl":"10.1016/j.rare.2025.100067","url":null,"abstract":"<div><div>Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome. Patients with LFS are at increased risk of early-onset tumours and undergo intensive radiological imaging surveillance to improve the early identification of malignancies. This report of a single-centre experience has shown that through surveillance imaging, especially whole-body MRIs, there is a high incidence of incidental findings. Incidental findings can result in anxiety and further evaluation often in the form of radiological imaging. It is important that patients and families are clearly counselled about incidental findings and findings of unknown clinical significance when undergoing imaging as part of a surveillance programme.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“True Faces of Rare”: Preferences for authentic imagery in disorder-specific materials by people living with rare diseases and their communities","authors":"Laura Smith van Carroll ,&nbsp;Pavel Krepelka ,&nbsp;Kirsty Hoyle ,&nbsp;Kamran Iqbal ,&nbsp;Tom Kenny","doi":"10.1016/j.rare.2025.100070","DOIUrl":"10.1016/j.rare.2025.100070","url":null,"abstract":"<div><div>This study explores the preferences of people living with rare diseases and their communities regarding the use of authentic imagery in disorder-specific materials. Through a digital survey of 50 respondents, we examined the perceived importance of using images of people affected by a rare disorder in educational and awareness materials about their specific disorder. Results reveal a strong preference for authentic imagery, with most respondents rating this as highly important. People living with rare diseases expressed that seeing “real faces” of those with the condition fosters a sense of connection, combats isolation, and raises public awareness through greater exposure. Conversely, some respondents noted the risk of stereotyping based on appearance, indicating the need for sensitive, accurate portrayal. Our findings suggest that authentic imagery can improve engagement and create an emotional connection with materials, by those living with rare diseases and their communities. Furthermore, we provide actionable recommendations for developers of these materials including patient advocacy groups, research institutions and pharmaceutical companies.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author’s response to “Correspondence on First year result and insights from the Mexican Rare Disease Patient Registry”","authors":"Claudia Gonzaga-Jauregui","doi":"10.1016/j.rare.2025.100075","DOIUrl":"10.1016/j.rare.2025.100075","url":null,"abstract":"","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of clinical outcomes and safety profile of trientine and d-penicillamine in the management of Wilson’s disease: A systematic review and meta-analysis","authors":"Hafiz Muhammad Ehsan Arshad,&nbsp;Muhammad Zain Raza,&nbsp;Musab Maqsood,&nbsp;Muhammad Omais,&nbsp;Muhammad Hashim Faisal,&nbsp;Ali Ahmad Nadeem","doi":"10.1016/j.rare.2025.100077","DOIUrl":"10.1016/j.rare.2025.100077","url":null,"abstract":"<div><h3>Introduction</h3><div>Wilson disease (WD) is a rare metabolic disorder of copper metabolism, requiring life-long therapy, usually with D-penicillamine or trientine. This review compares their clinical effectiveness and safety.</div></div><div><h3>Methodology</h3><div>PubMed, Cochrane, Clinicaltrials.gov and WHO-ICTRP, along with other sources were searched. The cohorts and RCTs reporting WD patients of any age or stage, receiving either trientine or D-penicillamine, were included. The Mantel-Haenszel method along with either a fixed- or random-effects model was used for analysing dichotomous outcomes.</div></div><div><h3>Results</h3><div>Twenty-six cohorts and one RCT were included. The odds of having (1) treatment failures were greater with trientine (OR = 4.09; 95 %-CI:2.34–7.15; p &lt; 0.00001); (2) adverse events were lesser with trientine (OR = 0.34; 95 %-CI:0.14–0.80; p = 0.01); (3) treatment discontinuation due to adverse events were lesser with trientine (OR = 0.30; 95 %-CI:0.21–0.43; p &lt; 0.00001); and (4) symptomatic worsening were not significantly different (OR = 1.68; 95 %-CI:0.88–3.20; p = 0.012). Subgroup analysis within symptomatic worsening showed non-significant difference for neurological worsening (OR = 1.33; 95 %-CI:0.44–3.97; p = 0.61) and greater odds with trientine for hepatic worsening (OR = 2.45; 95 %-CI:1.17–5.12; p = 0.02). Trientine had similar serum copper parameters and slightly lower urinary copper-excretion rates compared to D-penicillamine. Trientine affected coagulation profiles but with no clinical association, and both treatments had similar effects on pregnancy outcomes.</div></div><div><h3>Conclusion</h3><div>Trientine therapy had significantly lower incidences of adverse events and treatment discontinuations, but higher incidences of treatment failure and neurological worsening compared to D-penicillamine. However, the low quality and indirectness of the evidence may have lowered the validity of the results. Studies directly comparing the clinical outcomes of both treatments are needed to establish more robust evidence.</div></div>","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlights of the UDNI’s 12th International Conference (Tbilisi, Georgia, 2023)","authors":"Oleg Kvlividze,&nbsp;Tinatin (Tika) Tkemaladze","doi":"10.1016/j.rare.2025.100062","DOIUrl":"10.1016/j.rare.2025.100062","url":null,"abstract":"","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report of two cases of snRNA gene RNU4-2 related syndromic intellectual disability from Southeast Asia","authors":"Jeannette Goh ,&nbsp;Jiin Ying Lim ,&nbsp;Annet Simons ,&nbsp;Lisa Ewans ,&nbsp;Sylvia Kam ,&nbsp;Jasmine Goh ,&nbsp;Jing Xian Teo ,&nbsp;Sock Hoai Chan ,&nbsp;Shermaine Chan ,&nbsp;Simon Ling ,&nbsp;Terrence Thomas ,&nbsp;Gavin Tan ,&nbsp;Weng Khong Lim ,&nbsp;Angeline Lai ,&nbsp;Saumya Shekhar Jamuar","doi":"10.1016/j.rare.2024.100054","DOIUrl":"10.1016/j.rare.2024.100054","url":null,"abstract":"","PeriodicalId":101058,"journal":{"name":"Rare","volume":"3 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143133438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}